Parkinson's disease (PD) affects at least a half million Americans, and more as our population ages. Symptomatic medications can dramatically improve the lives of patients initially. However, with time disabling and unpredictable motor fluctuations occur, and the disease relentlessly progresses in most to dementia and immobility in the end stages. Therapy that slows progression of disease (neuroprotection) is desperately needed for the many thousands of affected Americans. In an effort to develop neuroprotective therapy the NINDS funded the NIH Exploratory Trials in PD (NET- PD) program, which consists of a Clinical Trials Coordination Center, a Statistical Center and 50 Clinical Sites. To date the NET-PD program has successfully completed four futility trials, is currently conducting a fifth futility trial (pioglitazone), and is in the process of completing a large simple (LSI) Phase III randomized, double-blinded, placebo-controlled clinical trial (creatine). These activities have contributed valuable scientific advances to the PD community. Our site, the University of Colorado Denver (UCD), is one of 50 selected Clinical Sites. The current NET-PD trials are expected to take three more years to complete; this application is a request for funding to complete the trials. Recruitment and retention of subjects at the Clinical Sites will be crucial fo success. The Specific Aims for the UCD site are (1) to complete the LSI study with retention of >85% of subjects and with >75% active in Study and on study drug, and (2) to do so with high adherence to study protocol and regulatory requirements. The UCD site has contributed greatly to the current success of the NET-PD program. For example, in LSI UCD is the fourth highest enrolling site and is the ninth highest in terms of retention of subjects on study drug. Dr. Leehey serves on the NET-PD program's Recruitment & Retention Committee and thus helped develop severally strategies that most sites employ to maximize recruitment and retention. Our site enters data and handles queries in a more reliable and timely fashion than average for all 50 sites. UCD has a number of strengths detailed in this application, including individualized expert care to subjects, which underlie our success and the reason our site is a strong and necessary asset to the NET-PD program.